The C-terminal of CASY-1/Calsyntenin regulates GABAergic synaptic transmission at the Caenorhabditis elegans neuromuscular junction
Fig 9
Proposed model for CASY-1 functioning at the NMJ.
CASY-1B and CASY-1C, the shorter isoforms are present on the SV precursors. The conserved C-terminal of CASY-1 act as an adaptor to mediate interaction of GABA-specific SVs with the tail region of UNC-104/KIF1A motor protein that mediates fast anterograde axonal transport of synaptic cargo. Mobility dynamics of SV precursors in turn regulates the release kinetics of GABA at NMJ. However in the absence of casy-1, this cargo-adaptor-motor bridge is lost resulting in aberrant anterograde flux of the GABA-specific SV cargo along the axonal pathway. This function of CASY-1B/C shows some similarity to how the mammalian CLSTN1 is thought to function. CLSTN1 has been shown to be required for fast anterograde axonal transport and loss of interaction with kinesin motor results in decreased anterograde trafficking and an increase in retrograde transport of vesicular cargo [18].